Ohkubo K, Baraniuk J N, Merida M, Hausfeld J N, Okada H, Kaliner M A
Department of Otolaryngology, Nippon Medical School, Tokyo, Japan.
J Allergy Clin Immunol. 1995 Dec;96(6 Pt 1):924-31. doi: 10.1016/s0091-6749(95)70230-x.
Carboxypeptidases (CPs), such as carboxypeptidase N (CPN) (kininase I, E.C.3.4.17.3), may regulate peptide-mediated vasodilation and vascular permeability in respiratory mucosa by degrading proinflammatory peptides such as bradykinin, anaphylatoxins, and neuropeptides during allergic and nonallergic inflammation. The sources of CP activity in human nasal secretions were investigated.
Well-characterized human nasal provocation and secretion analysis methods were used. Potential sources of CPN in human nasal mucosa were identified by immunohistochemistry. CP activity was defined as DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid inhibitable Bz-Gly-Lys degradation. CP activity was measured in nasal mucosal homogenates and nasal lavage fluids induced by methacholine, histamine, and allergen nasal provocation.
CPN-immunoreactive material was localized to the glycocalyx of the epithelium, some vessels, and gland ducts near the epithelial basement membrane but not to submucosal gland cells. CP activity in human nasal lavage fluid after saline nasal provocation was 0.10 +/- 0.04 U/L. Histamine provoked secretion of significantly more CP activity (3.84 +/- 0.99 U/L; p < 0.01 vs saline). Methacholine did not significantly increase secretion (0.54 +/- 0.22 U/L). After nasal allergen challenge, CP activity was at a maximum between 11 and 20 minutes, and CP activity correlated with IgG concentration (r = 0.91, p < 0.01), a marker for proteins of plasma origin, suggesting that CP activity originated in plasma.
These data suggest that plasma is the predominant source of CP activity secreted from human nasal mucosa and that plasma extravasation and interstitial fluid exudation across the epithelium are the primary processes regulating its appearance in nasal secretions.
羧肽酶（CPs），如羧肽酶N（CPN）（激肽酶I，E.C.3.4.17.3），可能通过在过敏性和非过敏性炎症期间降解促炎肽，如缓激肽、过敏毒素和神经肽，来调节呼吸道黏膜中肽介导的血管舒张和血管通透性。本研究调查了人鼻分泌物中CP活性的来源。
采用特征明确的人鼻激发试验和分泌物分析方法。通过免疫组织化学鉴定人鼻黏膜中CPN的潜在来源。CP活性定义为可被DL-2-巯基甲基-3-胍基乙基硫代丙酸抑制的Bz-Gly-Lys降解。在由乙酰甲胆碱、组胺和变应原鼻激发诱导的鼻黏膜匀浆和鼻灌洗液中测量CP活性。
CPN免疫反应性物质定位于上皮细胞的糖萼、一些血管以及上皮基底膜附近的腺管，但不存在于黏膜下腺细胞中。盐水鼻激发后人鼻灌洗液中的CP活性为0.10±0.04 U/L。组胺激发后分泌的CP活性显著增加（3.84±0.99 U/L；与盐水相比，p<0.01）。乙酰甲胆碱未显著增加分泌（0.54±0.22 U/L）。鼻变应原激发后，CP活性在11至20分钟之间达到最大值，且CP活性与IgG浓度相关（r = 0.91，p<0.01），IgG是血浆来源蛋白的标志物，提示CP活性起源于血浆。
这些数据表明，血浆是人鼻黏膜分泌的CP活性的主要来源，血浆外渗和上皮间的组织液渗出是调节其在鼻分泌物中出现的主要过程。
